Unacylated Ghrelin Does Not Acutely Affect Substrate Metabolism or Insulin Sensitivity in Men With Type 2 Diabetes

• Published in: The journal of clinical endocrinology and metabolism 2019-06, Vol.104 (6), p.2435-2442
• Main Authors: Vestergaard, Esben Thyssen, Jessen, Niels, Møller, Niels, Jørgensen, Jens Otto Lunde
• Format: Article
• Language: English
• Subjects: Acylation; Adult; Calorimetry; Clinical trials; Cross-Over Studies; Dextrose; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - metabolism; Double-Blind Method; Energy expenditure; Energy Metabolism; Ethylenediaminetetraacetic acid; Fatty acids; Ghrelin; Ghrelin - pharmacology; Glucose; Glucose - metabolism; Humans; Insulin; Insulin Resistance; Intravenous administration; Lipid metabolism; Lipolysis; Male; Medical research; Medicine, Experimental; Metabolism; Middle Aged; Oxidation; Respiration; Tracers (Biology); Type 2 diabetes
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2018-02601

Abstract Objective Unacylated ghrelin (UAG) is suggested to improve insulin sensitivity and may have therapeutic potential. We therefore tested the effects of intravenous UAG infusion on glucose and lipid metabolism, insulin sensitivity, and energy expenditure in men with type 2 diabetes mellitus (T2DM). Design Randomized, double-blind, placebo-controlled crossover study performed at a university hospital clinical research center. Methods Ten men with T2DM completed two study days: (i) 6-hour UAG infusion (1 µg/kg/h) and (ii) 6-hour placebo infusion. The patients were investigated in the basal postabsorptive state for 4 hours, followed by a hyperinsulinemic clamp for 2 hours. The turnover rates of glucose and fatty acids were assayed by isotope tracer techniques. Energy expenditure was measured by indirect calorimetry. Results The mean plasma UAG was 64.1 ± 11.3 pg/mL at baseline and increased >50-fold during UAG infusion. Plasma glucose was 7.0 ± 0.3 mmol/L during UAG infusion vs 6.7 ± 0.4 mmol/L placebo infusion (P = 0.43) at baseline and was not affected by UAG. During the hyperinsulinemic clamp, glucose infusion rates were 4.69 ± 0.56 mg/kg/min during UAG infusion vs 4.98 ± 0.43 mg/kg/min during placebo infusion (P = 0.66). UAG did not affect glucose oxidation, nonoxidative glucose disposal, lipolysis, energy expenditure, or respiratory exchange rate. Conclusions This study found that native UAG exposure did not exert acute metabolic effects in men with T2DM. Intravenous infusion of UAG for 6 hours did not affect plasma glucose, insulin sensitivity, lipolysis, or energy expenditure in men with T2DM.